title: Anxiety states induced by post-weaning social isolation are mediated by CRF receptors in the dorsal raphe nucleus.
abstract: Post-weaning social isolation of rats is utilized as a model of early life stress. We have previously demonstrated that rats exposed to post-weaning social isolation exhibit greater anxiety-like behaviors as adults. Furthermore, these rats exhibit greater density of corticotropin-releasing factor (CRF) type 2 receptors in the dorsal raphe nucleus. Therefore, we examined whether antagonism of CRF(2) receptors in the dorsal raphe nucleus reverses the effects of post-weaning social isolation on anxiety states. Male rats were reared in isolation or in groups from day of weaning (postnatal day [PND] 21) to mid-adolescence (PND42) and then allowed to develop to early adulthood housed in groups. At PND62, rats were either infused with vehicle, the CRF(1) receptor antagonist antalarmin (0.25-0.5 μg) or the CRF(2) receptor antagonist antisauvagine-30 (2 μg) into the dorsal raphe nucleus, 20 min prior to being introduced to the elevated plus maze. Isolation-reared rats showed reduced open arm behavior compared to group-reared rats, confirming the anxiogenic effects of post-weaning social isolation. Infusion of the CRF(2) receptor antagonist, but not the CRF(1) receptor antagonist, into the dorsal raphe nucleus of isolation-reared rats increased open arm behavior when compared to that of group-reared rats. Overall, the findings suggest that CRF(2) receptors within the dorsal raphe nucleus mediate anxiety-like states following post-weaning social isolation, and CRF(2) receptors may represent an important target for the treatment of anxiety disorders following early life stressors.
authors.affiliation: Neuroscience Group, Division of Basic Biomedical Sciences, Sanford School of Medicine, The University of South Dakota, 414 E Clark St, Vermillion, SD 57069, USA.
authors.forename: Adam C
authors.initials: AC
authors.lastname: Bledsoe
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Oliver
authors.forename: Jamie L
authors.initials: JL
authors.lastname: Scholl
authors.forename: Gina L
authors.initials: GL
authors.lastname: Forster
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001007:Anxiety / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D010446:Peptide Fragments / Q000008:administration & dosage; D011743:Pyrimidines / Q000008:administration & dosage; D011758:Pyrroles / Q000008:administration & dosage; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018019:Receptors, Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012934:Social Isolation / Q000523:psychology*
chemical_list: C101531:CRF receptor type 2; D010446:Peptide Fragments; D011743:Pyrimidines; D011758:Pyrroles; D018019:Receptors, Corticotropin-Releasing Hormone; C103016:antalarmin; C116607:antisauvagine 30